1. The constituents and functional implications of default mode network in the rat brain The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation within the network. Because preclinical models can inform translational studies of neuropsychiatric disorders, partitioning of the DMN in nonhuman species, which has previously not been reported, may inform both physiology and pathophysiology of the human DMN. In this study, we sought to identify constituents of the rat DMN using resting-state functional MRI (rs-fMRI) and diffusion tensor imaging. After identifying DMN using a group-level independent-component analysis on the rs-fMRI data, modularity analyses fractionated the DMN into an anterior and a posterior subsystem, which were further segregated into five modules. Diffusion tensor imaging tractography demonstrates a close relationship between fiber density and the functional connectivity between DMN regions, and provides anatomical evidence to support the detected DMN subsystems. Finally, distinct modulation was seen within and between these DMN subcomponents using a neurocognitive aging model. Taken together, these results suggest that, like the human DMN, the rat DMN can be partitioned into several subcomponents that may support distinct functions. These data encourage further investigation into the neurobiological mechanisms of DMN processing in preclinical models of both normal and disease states. (Hsu et al., PNAS, 2016) 2. Physiological characterization of a robust survival rodent fMRI method Anesthetics are commonly used in preclinical functional MRI studies. It is well appreciated that proper choice of anesthetics is of critical importance for maintaining a physiologically normal range of autonomic functioning. A recent study, using a low dose of dexmedetomidine (active isomer of medetomidine) in combination with a low dose of isoflurane, suggested stable measurements across repeated fMRI experiments in individual animals with each session lasting up to several hours. The rat default mode network has been successfully identified using this preparation, indicating that this protocol minimally disturbs brain network functions. However, medetomidine is known to cause peripheral vasoconstriction, respiratory suppression, and bradycardia, each of which could independently confound the BOLD signal. The goal of this study was to systematically characterize physiological conditions for fMRI experiments under this anesthetic regime. To this end, we acquired somatosensory stimulation task-evoked and resting-state fMRI to evaluate the integrity of neurovascular coupling and brain network function during three time windows (0-30 min, 30-90 min, and 90-150 min) following dexmedetomidine initiation. Results demonstrate that both evoked BOLD response and resting-state fMRI signal remained stable during the 90-150 min time window, while autonomic physiological parameters maintained near normal condition during this period. Our data suggest that a spontaneously-inhaled, low dose of isoflurane in combination with a continuous low dose of dexmedetomidine is a viable option for longitudinal imaging studies in rats. (Brynildsen et al., Magn Reson Imag, accepted) 3. Neurophysiological basis of resting state functional connectivity Spontaneous ongoing activity is a prominent feature of the mammalian brain. Temporal and spatial patterns of such ongoing activity have been exploited to form brain networks that reflect large-scale brain operation. However, the neurophysiological basis of spontaneous brain activity as detected by resting-state functional magnetic resonance imaging (fMRI) remains poorly understood. To this end, multi-site local field potentials (LFP) and functional magnetic resonance imaging (fMRI) were simultaneously recorded in the rat striatum along with pharmacological manipulation of striatal activity. Results demonstrate that band LFP power negatively, while , band LFP positively correlate with BOLD fluctuation. Further, there was strong cross-frequency phase-amplitude coupling (PAC), with the phase of LFP significantly modulating the amplitude of the high frequency signal. Enhancing dopaminergic neuronal activity significantly reduced ventral striatal functional connectivity, LFP-BOLD correlation, and PAC effect. Our data suggest that LFP of different frequency bands contribute distinctively to BOLD fluctuation and that PAC effect is the organizing mechanism through which low frequency LFP orchestrates neural activity that underlies the resting state functional connectivity. (Manuscript submitted for publication) 4. Development of focused magnetic field for non-invasive brain stimulation in the rat brain Transcranial magnetic stimulation (TMS) is one of the most widely used methods for brain stimulation. It is utilized in the treatment of many neurological and psychiatric diseases, such as depression and drug addiction. Current commercial TMS stimulators cannot provide well targeted stimulation, particularly in small animals. Due to fast field divergence, the effective distance in TMS is limited to around 1.5 cm. We demonstrated the use magnetic shield to achieve magnetic focusing without sacrificing significant amount of throughput. The shield is composed of multiple layers of copper ring arrays, which utilize induced current in the ring to generate counter magnetic fields. We experimentally set up a two pole stimulator system. A transient magnetic field probe was used for field measurements. The shield effect not only depends on the design of shield structure but also the intensity of original magnetic field from the stimulator. A higher original magnetic field can produce stronger counter field and achieve better focusing. A tight focal spot with a diameter of 0.5cm was achieved by using 4 layers of copper ring arrays. Such a multilayer based shield structure will be tested in targeted noninvasive stimulation of the rat brain. (Manuscript submitted for publication).